Cholesterol homeostasis and hepatocyte sensors

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Role of bile acids in cholesterol regulation, digestion & metabolic diseases like diabetes.

TOPICS DISCUSSED:

• Bile acids basics: They enable cholesterol excretion, with about half of bodily cholesterol eliminated this way, and also aid digestion by emulsifying fats to increase enzyme access.
• Bile production & pathway: Synthesized in liver hepatocytes, bile flows via ducts to the gallbladder for storage or directly to the small intestine; post-meal, cholecystokinin triggers gallbladder contraction for fat emulsification.
• Regulation of bile acids: Self-regulated to prevent cytotoxicity, as excess can damage cell membranes; insulin and bile acids themselves influence synthesis and transport, with defects in insulin-resistant states.
• Bile acids in metabolic diseases: Increased synthesis, especially 12-hydroxylated types, occurs in type 2 diabetes and insulin resistance, potentially as an adaptation for better nutrient absorption during perceived scarcity.
• Gallbladder removal & gallstones: Common due to cholesterol supersaturation forming stones; removal eliminates concentration but preserves bile flow, reducing tolerance for high-fat meals.
• Bariatric surgery impacts: Procedures like gastric bypass increase circulating bile acids without major synthesis changes, while more extreme ones boost synthesis due to impaired intestinal sensing.
• Cholesterol homeostasis: Cells tightly regulate membrane cholesterol for fluidity and signaling; most bodily cholesterol is synthesized internally, with LDL receptors key to blood levels.
• Ongoing research: Haeusler’s lab explores manganese’s role in metabolism, bile acids in liver inflammation, and insulin’s effects on lipoproteins.

ABOUT THE GUEST: Rebecca Haeusler, PhD is an associate professor at Columbia University in the departments of medicine and pathology and cell biology, affiliated with the Naomi Berrie Diabetes Center and the Digestive and Liver Diseases Research Center.

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